An Implantable Ultrasonically-Powered Micro-Light-Source (µLight) for Photodynamic Therapy
Photodynamic therapy (PDT) is a promising cancer treatment modality that can selectively target unresectable tumors through optical activation of cytotoxic agents, thus reducing many side effects associated with systemic administration of chemotherapeutic drugs. However, limited light penetration in...
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description | Photodynamic therapy (PDT) is a promising cancer treatment modality that can selectively target unresectable tumors through optical activation of cytotoxic agents, thus reducing many side effects associated with systemic administration of chemotherapeutic drugs. However, limited light penetration into most biological tissues have so far prevented its widespread adoption beyond dermatology and a few other oncological applications in which a fiber optic can be threaded to the desired locations via an endoscopic approach (e.g., bladder). In this paper, we introduce an ultrasonically powered implantable microlight source, μLight, which enables
in-situ
localized light delivery to deep-seated solid tumors. Ultrasonic powering allows for small receiver form factor (mm-scale) and power transfer deep into the tissue (several centimeters). The implants consist of piezoelectric transducers measuring 2 × 2 × 2 mm
3
and 2 × 4 × 2 mm
3
with surface-mounted miniature red and blue LEDs. When energized with 185 mW/cm
2
of transmitted acoustic power at 720 kHz, μLight can generate 0.048 to 6.5 mW/cm
2
of optical power (depending on size of the piezoelectric element and light wavelength spectrum). This allows powering multiple receivers to a distance of 10 cm at therapeutic light output levels (a delivery of 20–40 J/cm
2
light radiation dose in 1–2 hours).
In vitro
tests show that HeLa cells irradiated with μLights undergo a 70% decrease in average cell viability as compared to the control group.
In vivo
tests in mice implanted with 4T1-induced tumors (breast cancer) show light delivery capability at therapeutic dose levels. Overall, results indicate implanting multiple µLights and operating them for 1–2 hours can achieve cytotoxicity levels comparable to the clinically reported cases using external light sources. |
doi_str_mv | 10.1038/s41598-019-38554-2 |
format | Article |
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in-situ
localized light delivery to deep-seated solid tumors. Ultrasonic powering allows for small receiver form factor (mm-scale) and power transfer deep into the tissue (several centimeters). The implants consist of piezoelectric transducers measuring 2 × 2 × 2 mm
3
and 2 × 4 × 2 mm
3
with surface-mounted miniature red and blue LEDs. When energized with 185 mW/cm
2
of transmitted acoustic power at 720 kHz, μLight can generate 0.048 to 6.5 mW/cm
2
of optical power (depending on size of the piezoelectric element and light wavelength spectrum). This allows powering multiple receivers to a distance of 10 cm at therapeutic light output levels (a delivery of 20–40 J/cm
2
light radiation dose in 1–2 hours).
In vitro
tests show that HeLa cells irradiated with μLights undergo a 70% decrease in average cell viability as compared to the control group.
In vivo
tests in mice implanted with 4T1-induced tumors (breast cancer) show light delivery capability at therapeutic dose levels. Overall, results indicate implanting multiple µLights and operating them for 1–2 hours can achieve cytotoxicity levels comparable to the clinically reported cases using external light sources.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/s41598-019-38554-2</identifier><identifier>PMID: 30718792</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13/107 ; 13/2 ; 13/21 ; 639/166/985 ; 639/166/987 ; Breast cancer ; Cell viability ; Cytotoxic agents ; Cytotoxicity ; Humanities and Social Sciences ; Light ; Light penetration ; Light sources ; multidisciplinary ; Photodynamic therapy ; Science ; Science (multidisciplinary) ; Side effects ; Solid tumors ; Transducers ; Tumors</subject><ispartof>Scientific reports, 2019-02, Vol.9 (1), p.1395-1395, Article 1395</ispartof><rights>The Author(s) 2019</rights><rights>This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c579t-6ba5268892ffeb4564a9e896671e08b63fc810d064a506d0fac28f30d599ffdf3</citedby><cites>FETCH-LOGICAL-c579t-6ba5268892ffeb4564a9e896671e08b63fc810d064a506d0fac28f30d599ffdf3</cites><orcidid>0000-0002-0746-1526</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6362227/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6362227/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27901,27902,41096,42165,51551,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30718792$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kim, Albert</creatorcontrib><creatorcontrib>Zhou, Jiawei</creatorcontrib><creatorcontrib>Samaddar, Shayak</creatorcontrib><creatorcontrib>Song, Seung Hyun</creatorcontrib><creatorcontrib>Elzey, Bennet D.</creatorcontrib><creatorcontrib>Thompson, David H.</creatorcontrib><creatorcontrib>Ziaie, Babak</creatorcontrib><title>An Implantable Ultrasonically-Powered Micro-Light-Source (µLight) for Photodynamic Therapy</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>Photodynamic therapy (PDT) is a promising cancer treatment modality that can selectively target unresectable tumors through optical activation of cytotoxic agents, thus reducing many side effects associated with systemic administration of chemotherapeutic drugs. However, limited light penetration into most biological tissues have so far prevented its widespread adoption beyond dermatology and a few other oncological applications in which a fiber optic can be threaded to the desired locations via an endoscopic approach (e.g., bladder). In this paper, we introduce an ultrasonically powered implantable microlight source, μLight, which enables
in-situ
localized light delivery to deep-seated solid tumors. Ultrasonic powering allows for small receiver form factor (mm-scale) and power transfer deep into the tissue (several centimeters). The implants consist of piezoelectric transducers measuring 2 × 2 × 2 mm
3
and 2 × 4 × 2 mm
3
with surface-mounted miniature red and blue LEDs. When energized with 185 mW/cm
2
of transmitted acoustic power at 720 kHz, μLight can generate 0.048 to 6.5 mW/cm
2
of optical power (depending on size of the piezoelectric element and light wavelength spectrum). This allows powering multiple receivers to a distance of 10 cm at therapeutic light output levels (a delivery of 20–40 J/cm
2
light radiation dose in 1–2 hours).
In vitro
tests show that HeLa cells irradiated with μLights undergo a 70% decrease in average cell viability as compared to the control group.
In vivo
tests in mice implanted with 4T1-induced tumors (breast cancer) show light delivery capability at therapeutic dose levels. Overall, results indicate implanting multiple µLights and operating them for 1–2 hours can achieve cytotoxicity levels comparable to the clinically reported cases using external light sources.</description><subject>13/107</subject><subject>13/2</subject><subject>13/21</subject><subject>639/166/985</subject><subject>639/166/987</subject><subject>Breast cancer</subject><subject>Cell viability</subject><subject>Cytotoxic agents</subject><subject>Cytotoxicity</subject><subject>Humanities and Social Sciences</subject><subject>Light</subject><subject>Light penetration</subject><subject>Light sources</subject><subject>multidisciplinary</subject><subject>Photodynamic therapy</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>Side effects</subject><subject>Solid tumors</subject><subject>Transducers</subject><subject>Tumors</subject><issn>2045-2322</issn><issn>2045-2322</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>BENPR</sourceid><recordid>eNp9Ud1OHCEYJY2mmtUX6EUzSW_sBQofAwM3TcymrSZrNKleeUEYBnbHzAwrzNrsg_kCPlnRtf70otzAx3e-A-cchD5RckgJk0eppFxJTKjCTHJeYviAdoGUHAMD2Hpz3kH7Kd2QvDiokqqPaIeRispKwS66Ph6K037ZmWE0deeKq26MJoWhtabr1vgi_HbRNcVZa2PAs3a-GPGvsIrWFQcP90_118KHWFwswhia9WD61haXCxfNcr2Htr3pktt_3ifo6sf3y-kJnp3_PJ0ez7DllRqxqA0HIaUC711dclEa5aQSoqKOyFowbyUlDcn3nIiGeGNBekYarpT3jWcT9G3Du1zVvWusG7KGTi9j25u41sG0-n1naBd6Hu60YAIAqkxw8EwQw-3KpVH3bbKuy664sEoaaKV4ySgnGfrlH-hNtmPI8jSw3AdZiUcUbFDZtZSi8y-foUQ_xqc38ekcn36KL09P0Oe3Ml5G_oaVAWwDSLk1zF18ffs_tH8AlWmm1A</recordid><startdate>20190204</startdate><enddate>20190204</enddate><creator>Kim, Albert</creator><creator>Zhou, Jiawei</creator><creator>Samaddar, Shayak</creator><creator>Song, Seung Hyun</creator><creator>Elzey, Bennet D.</creator><creator>Thompson, David H.</creator><creator>Ziaie, Babak</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>C6C</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-0746-1526</orcidid></search><sort><creationdate>20190204</creationdate><title>An Implantable Ultrasonically-Powered Micro-Light-Source (µLight) for Photodynamic Therapy</title><author>Kim, Albert ; Zhou, Jiawei ; Samaddar, Shayak ; Song, Seung Hyun ; Elzey, Bennet D. ; Thompson, David H. ; Ziaie, Babak</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c579t-6ba5268892ffeb4564a9e896671e08b63fc810d064a506d0fac28f30d599ffdf3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>13/107</topic><topic>13/2</topic><topic>13/21</topic><topic>639/166/985</topic><topic>639/166/987</topic><topic>Breast cancer</topic><topic>Cell viability</topic><topic>Cytotoxic agents</topic><topic>Cytotoxicity</topic><topic>Humanities and Social Sciences</topic><topic>Light</topic><topic>Light penetration</topic><topic>Light sources</topic><topic>multidisciplinary</topic><topic>Photodynamic therapy</topic><topic>Science</topic><topic>Science (multidisciplinary)</topic><topic>Side effects</topic><topic>Solid tumors</topic><topic>Transducers</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kim, Albert</creatorcontrib><creatorcontrib>Zhou, Jiawei</creatorcontrib><creatorcontrib>Samaddar, Shayak</creatorcontrib><creatorcontrib>Song, Seung Hyun</creatorcontrib><creatorcontrib>Elzey, Bennet D.</creatorcontrib><creatorcontrib>Thompson, David H.</creatorcontrib><creatorcontrib>Ziaie, Babak</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kim, Albert</au><au>Zhou, Jiawei</au><au>Samaddar, Shayak</au><au>Song, Seung Hyun</au><au>Elzey, Bennet D.</au><au>Thompson, David H.</au><au>Ziaie, Babak</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>An Implantable Ultrasonically-Powered Micro-Light-Source (µLight) for Photodynamic Therapy</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2019-02-04</date><risdate>2019</risdate><volume>9</volume><issue>1</issue><spage>1395</spage><epage>1395</epage><pages>1395-1395</pages><artnum>1395</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>Photodynamic therapy (PDT) is a promising cancer treatment modality that can selectively target unresectable tumors through optical activation of cytotoxic agents, thus reducing many side effects associated with systemic administration of chemotherapeutic drugs. However, limited light penetration into most biological tissues have so far prevented its widespread adoption beyond dermatology and a few other oncological applications in which a fiber optic can be threaded to the desired locations via an endoscopic approach (e.g., bladder). In this paper, we introduce an ultrasonically powered implantable microlight source, μLight, which enables
in-situ
localized light delivery to deep-seated solid tumors. Ultrasonic powering allows for small receiver form factor (mm-scale) and power transfer deep into the tissue (several centimeters). The implants consist of piezoelectric transducers measuring 2 × 2 × 2 mm
3
and 2 × 4 × 2 mm
3
with surface-mounted miniature red and blue LEDs. When energized with 185 mW/cm
2
of transmitted acoustic power at 720 kHz, μLight can generate 0.048 to 6.5 mW/cm
2
of optical power (depending on size of the piezoelectric element and light wavelength spectrum). This allows powering multiple receivers to a distance of 10 cm at therapeutic light output levels (a delivery of 20–40 J/cm
2
light radiation dose in 1–2 hours).
In vitro
tests show that HeLa cells irradiated with μLights undergo a 70% decrease in average cell viability as compared to the control group.
In vivo
tests in mice implanted with 4T1-induced tumors (breast cancer) show light delivery capability at therapeutic dose levels. Overall, results indicate implanting multiple µLights and operating them for 1–2 hours can achieve cytotoxicity levels comparable to the clinically reported cases using external light sources.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>30718792</pmid><doi>10.1038/s41598-019-38554-2</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0002-0746-1526</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | 13/107 13/2 13/21 639/166/985 639/166/987 Breast cancer Cell viability Cytotoxic agents Cytotoxicity Humanities and Social Sciences Light Light penetration Light sources multidisciplinary Photodynamic therapy Science Science (multidisciplinary) Side effects Solid tumors Transducers Tumors |
title | An Implantable Ultrasonically-Powered Micro-Light-Source (µLight) for Photodynamic Therapy |
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